MicroRNA-17 Modulates Regulatory T Cell Function by Targeting Co-regulators of the Foxp3 Transcription Factor.

Regulatory T (Treg) cells are important in maintaining self-tolerance and immune homeostasis. The Treg cell transcription factor Foxp3 works in concert with other co-regulatory molecules, including Eos, to determine the transcriptional signature and characteristic suppressive phenotype of Treg cells. Here, we report that the inflammatory cytokine interleukin-6 (IL-6) actively repressed Eos expression through microRNA-17 (miR-17). miR-17 expression increased in Treg cells in the presence of IL-6, and its expression negatively correlated with that of Eos. Treg cell suppressive activity was diminished upon overexpression of miR-17 in vitro and in vivo, which was mitigated upon co-expression of an Eos mutant lacking miR-17 target sites. Also, RNAi of miR-17 resulted in enhanced suppressive activity. Ectopic expression of miR-17 imparted effector-T-cell-like characteristics to Treg cells via the de-repression of genes encoding effector cytokines. Thus, miR-17 provides a potent layer of Treg cell control through targeting Eos and additional Foxp3 co-regulators.

Deaths of U.S. Citizens Undergoing Cosmetic Surgery - Dominican Republic, 2009-2022.

Although infections resulting from cosmetic surgery performed outside the United States have been regularly reported, deaths have rarely been identified. During 2009-2022, 93 U.S. citizens died after receiving cosmetic surgery in the Dominican Republic. The number of deaths increased from a mean of 4.1 per year during 2009-2018 to a mean of 13.0 during 2019-2022 with a peak in of 17 in 2020. A subset of post-cosmetic surgery deaths occurring during peak years was investigated, and most deaths were found to be the result of embolic events (fat emboli or venous thromboembolism) for which a high proportion of the patients who died had risk factors, including obesity and having multiple procedures performed during the same operation. These risk factors might have been mitigated or prevented with improved surgical protocols and postoperative medical care, including prophylactic measures against venous thromboembolism. U.S. citizens interested in receiving elective cosmetic surgery outside the United States should consult with their health care professionals regarding their risk for adverse outcomes. Public health authorities can support provider education on the importance of preoperative patient evaluation and the potential danger of performing multiple cosmetic procedures in one operation.

Patterns of Perioperative Hormone Therapy for Gender-Affirming Surgery.

INTRODUCTION: There is no consensus regarding perioperative hormone replacement therapy (HRT) for gender-affirming surgery (GAS). Common concerns for continuing perioperative HRT included risk of deep vein thrombosis (DVT) or hematoma. However, discontinuing HRT is not risk free and may cause mood swing or increased anxiety. Our study aimed to investigate current patterns of HRT before GAS worldwide. METHODS: The first stage of Delphi technique was implemented by sending a 27-item survey to all surgeons (total n = 150; 94 plastic surgeon, 35 urologist, and 21 gynecologists) of the World Professional Association for Transgender Health who perform GAS. Survey themes included the hormone type, duration, and usage of DVT prophylaxis. RESULTS: Overall survey response rate was 34% (total n = 51; 8 urologists, 35 plastic surgeons, and 8 gynecologists). The majority of surgeons are US-based (n = 39, 76%). The most common HRTs are in injection form (n = 28, 55%). The majority of surgeons do not stop HRT before GAS and do provide DVT prophylaxis to all patients <1 week after GAS. The most common procedure that surgeons discontinue HRT is feminizing bottom surgery (43%). For surgeons who discontinue HRT before GAS, there is a wide variation on discontinuation schedule. CONCLUSIONS: There is considerable variation in perioperative HRT patterns for GAS. Further research is needed to develop a data-driven consensus guideline to provide high quality of care for transgender and nonbinary patients.

Checkpoint inhibitor-related myasthenia-myocarditis-myositis overlap syndrome in the orbit.

We report a series of three patients who developed checkpoint inhibitor-related myocarditis with orbital myositis and/or myasthenia gravis overlap syndrome, with varying degrees of severity. In all cases, checkpoint inhibitor therapy was immediately discontinued upon diagnosis and corticosteroids were initiated. While two patients achieved substantial recovery, one patient passed away on hospital day three. These cases underscore the critical need for prompt recognition of adverse events associated with immune checkpoint inhibitors.

High Burden of Intestinal Colonization With Antimicrobial-Resistant Bacteria in Chile: An Antibiotic Resistance in Communities and Hospitals (ARCH) Study.

BACKGROUND: Antimicrobial resistance is a global threat, heavily impacting low- and middle-income countries. This study estimated antimicrobial-resistant gram-negative bacteria (GNB) fecal colonization prevalence in hospitalized and community-dwelling adults in Chile before the coronavirus disease 2019 pandemic. METHODS: From December 2018 to May 2019, we enrolled hospitalized adults in 4 public hospitals and community dwellers from central Chile, who provided fecal specimens and epidemiological information. Samples were plated onto MacConkey agar with ciprofloxacin or ceftazidime added. All recovered morphotypes were identified and characterized according to the following phenotypes: fluoroquinolone-resistant (FQR), extended-spectrum cephalosporin-resistant (ESCR), carbapenem-resistant (CR), or multidrug-resistant (MDR; as per Centers for Disease Control and Prevention criteria) GNB. Categories were not mutually exclusive. RESULTS: A total of 775 hospitalized adults and 357 community dwellers were enrolled. Among hospitalized subjects, the prevalence of colonization with FQR, ESCR, CR, or MDR-GNB was 46.4% (95% confidence interval [CI], 42.9-50.0), 41.2% (95% CI, 37.7-44.6), 14.5% (95% CI, 12.0-16.9), and 26.3% (95% CI, 23.2-29.4). In the community, the prevalence of FQR, ESCR, CR, and MDR-GNB colonization was 39.5% (95% CI, 34.4-44.6), 28.9% (95% CI, 24.2-33.6), 5.6% (95% CI, 3.2-8.0), and 4.8% (95% CI, 2.6-7.0), respectively. CONCLUSIONS: A high burden of antimicrobial-resistant GNB colonization was observed in this sample of hospitalized and community-dwelling adults, suggesting that the community is a relevant source of antibiotic resistance. Efforts are needed to understand the relatedness between resistant strains circulating in the community and hospitals.

TRAF6 directs FOXP3 localization and facilitates regulatory T-cell function through K63-linked ubiquitination.

Regulatory T cells (Tregs) are crucial mediators of immune control. The characteristic gene expression and suppressive functions of Tregs depend considerably on the stable expression and activity of the transcription factor FOXP3. Transcriptional regulation of the Foxp3 gene has been studied in depth, but both the expression and function of this factor are also modulated at the protein level. However, the molecular players involved in posttranslational FOXP3 regulation are just beginning to be elucidated. Here, we found that TRAF6-deficient Tregs were dysfunctional in vivo; mice with Treg-restricted deletion of TRAF6 were resistant to implanted tumors and displayed enhanced anti-tumor immunity. We further determined that FOXP3 undergoes K63-linked ubiquitination at lysine 262 mediated by the E3 ligase TRAF6. In the absence of TRAF6 activity or upon mutation of the ubiquitination site, FOXP3 displayed aberrant, perinuclear accumulation and disrupted regulatory function. Thus, K63-linked ubiquitination by TRAF6 ensures proper localization of FOXP3 and facilitates the transcription factor's gene-regulating activity in Tregs. These results implicate TRAF6 as a key posttranslational, Treg-stabilizing regulator that may be targeted in novel tolerance-breaking therapies.

Multidimensional Assessment of Patient-Reported Outcomes After Gender-Affirming Surgeries Using a Validated Instrument.

INTRODUCTION: Limited literatures used validated instruments to evaluate patient-reported outcomes (PROs) for transgender and gender-diverse population undergoing gender-affirming surgeries (GASs). This study aimed to evaluate PROs using a newly validated psychometric instrument, Vanderbilt Mini Patient-Reported Outcome Measures-Gender (VMP-G). METHODS: Vanderbilt Mini Patient-Reported Outcome Measures-Gender assesses 4 scales: quality of life, self-concept, satisfaction, and gender dysphoria. Scores range from 20 to 100, with higher scores representing superior PROs. Descriptive analysis was performed, and outcomes were compared in different races/ethnicities, gender identities, age, types of GAS, and time. Patients seeking GAS at Vanderbilt University Medical Center from October 11, 2021, to October 11, 2022, were included. Data were collected anonymously via the Research Electronic Data Capture survey tool at preoperative or postoperative clinic visits. RESULTS: A total of 207 patients completed VMP-G. Average age was 31.8 years (SD, ±11.5 years). Fifty-three percent of patients were postoperative GAS. In bivariate and linear regression analyses, postoperative patients scored higher on all scales compared with preoperative patients ( P < 0.001). After adjustment, postoperative patients scored 12.5 higher on VMP-G compared with preoperative patients ( P < 0.01). In subset analyses, GAS was associated with improved PROs in White, non-White, binary, and nonbinary and patients younger than 21 years ( P < 0.05). After GAS, patients younger than 21 years reported similar outcomes, compared with patients older than 21 years ( P > 0.05). No PROs differences were reported between patients who underwent top versus bottom surgery ( P = 0.2). Postoperative patients reported low rates of regret (2.8%). Scores on the VMP-G were sustained even 1 year after GAS. Each month after GAS was associated with a score improvement of 0.02 in the gender dysphoria domain after adjusting for patient demographics ( P = 0.02). CONCLUSIONS: Using a validated GAS-specific measure, we found that surgery sustainably improves patients' self-reported outcomes including gender dysphoria.

Patient Perspectives on Selecting an Academic Aesthetic Surgeon: A Qualitative Analysis.

BACKGROUND: Growth of the aesthetic surgery marketplace has increased patient choice in provider selection. This study aimed to characterize how patients choose an aesthetic surgeon, identify knowledge gaps in this decision-making process, and understand why patients select academic aesthetic surgeons. METHODS: A qualitative interview study of aesthetic surgery patients from an academic center was conducted. Purposive sampling maximized representation regarding surgeon, surgery type, and patient demographics. An interview guide was developed in collaboration with content and methodology experts, then refined through pilot testing. Emergent themes were identified using a codebook constructed by grounded theory. RESULTS: Thematic saturation was achieved with 24 patients. When selecting a surgeon, participants valued bedside manner (24 of 24) and past patients' satisfaction (18 of 24). Most participants (16 of 24) ascribed low importance to board certification. Reasons given for choosing an academic practice included the institution's reputation (13 of 24) and the availability of medical records and other specialties if complications arise (8 of 24). Participants demonstrated knowledge gaps regarding medical training and licensure. No participant (0 of 24) was aware that any licensed physician can offer aesthetic surgery, and nearly all participants (23 of 24) expressed discomfort with this. CONCLUSIONS: Patients prioritize subjective elements when selecting an aesthetic surgeon, relying less on objective and meaningful qualifications like board certification and training background. Academic aesthetic practice is valued because of reputation and ability to function as a medical home. Given the lack of public understanding regarding physician training, initiatives promoting transparency are needed to ensure that patients can make safe, informed decisions.

Comparison of Complication Rates Between Subpectoral vs Prepectoral Techniques in Prosthetic Breast Reconstruction.

BACKGROUND: The location of tissue expanders in implant-based breast reconstruction remains controversial due to variation in surgical techniques and devices. OBJECTIVES: The aim of this study was to provide a comprehensive assessment of early and late complication rates between prepectoral and subpectoral placement of tissue expanders. METHODS: A retrospective cohort study was conducted of all adult female patients who had undergone 2-stage implant-based breast reconstruction between 2013 and 2019 in our institution. Early complication was defined as complications that occurred within 30 days after surgery. Time-to-event analyses were performed and Cox proportional hazard models were used to adjust for confounders. RESULTS: In total, 854 patients were included; 76% of patients underwent a subpectoral tissue expander placement. After the first-stage procedure, the early complication rate was 34% and the late complication rate was 36.4%. After the second-stage procedure, the early complication rate was 16.3% and the late complication rate was 16.1%. Location of the tissue expander did not predict either overall early or late complication rates, regardless of the stages of reconstruction, after adjusting for confounders. Tissue expanders placed in prepectoral plane were associated with a higher hazard ratio (HR) for developing early and late infection after the first stage of reconstruction (HR, 2.1 and 2.4, respectively) as well as late infection after the second stage of reconstruction (HR, 5.3; all P < .05). CONCLUSIONS: Location of tissue expanders did not predict risk of complication. However, the prepectoral group was associated with an increased risk of developing infection.

Infection Prevention and Control Initiatives to Prevent Healthcare-Associated Transmission of SARS-CoV-2, East Africa.

The coronavirus disease pandemic has highlighted the need to establish and maintain strong infection prevention and control (IPC) practices, not only to prevent healthcare-associated transmission of SARS-CoV-2 to healthcare workers and patients but also to prevent disruptions of essential healthcare services. In East Africa, where basic IPC capacity in healthcare facilities is limited, the US Centers for Disease Control and Prevention (CDC) supported rapid IPC capacity building in healthcare facilities in 4 target countries: Tanzania, Ethiopia, Kenya, and Uganda. CDC supported IPC capacity-building initiatives at the healthcare facility and national levels according to each country's specific needs, priorities, available resources, and existing IPC capacity and systems. In addition, CDC established a multicountry learning network to strengthen hospital level IPC, with an emphasis on peer-to-peer learning. We present an overview of the key strategies used to strengthen IPC in these countries and lessons learned from implementation.

Recurrence of Hypophysitis After Immune Checkpoint Inhibitor Rechallenge.

Immune checkpoint inhibitor (ICI)-induced hypophysitis is an immune-mediated pituitary inflammation that tends to cause long-term pituitary deficiency. Management of ICI-induced hypophysitis includes corticosteroids for acute inflammation and long-term hormone replacement due to irreversible pituitary cell damage. We report a case of recurrent hypophysitis following ICI rechallenge for metastatic melanoma. A 33-year-old woman with recurrent metastatic melanoma with adrenal, pelvic, and inguinal metastases developed recurrent hypophysitis during treatment with ipilimumab and nivolumab which recurred with rechallenge >5 years later. In both cases, headache was the most notable symptom and brain MRI showed pituitary enlargement and edema without evidence of metastases. Central adrenal insufficiency and symptoms caused by mass effect were treated with acute high-dose corticosteroids and long-term replacement corticosteroids. Based on recurrence and failure of symptomatic treatment with continued steroid treatment, ICI was discontinued. This case illustrates that hypophysitis may recur with ICI rechallenge, challenging traditional assumptions that chronic, irreversible irAEs are unlikely to recur or flare. The regenerative potential of pituitary cells after ICI-induced damage or additional damage to previously unaffected cells may be more conceivable than previously realized. Additional research on the potential for recurrent ICI-induced endocrinopathies are needed.

Immune checkpoint inhibitors and their impact on liver enzymes and attenuation.

BACKGROUND: Immune related adverse events impacting the liver are common from immune checkpoint inhibitor (ICI) therapy; however, there is little data regarding the subclinical impact of ICIs on liver inflammation. The study aims to determine whether ICI therapy affects liver attenuation and liver enzymes in melanoma patients with and without hepatic steatosis. METHODS: A retrospective, cohort study was conducted of patients with advanced melanoma treated with ICI therapy who received serial PET-CT scans at the Vanderbilt University Medical Center (VUMC). Primary outcomes included: liver attenuation measured by PET-CT/non-contrast CT and liver enzymes. Hepatic steatosis was diagnosed by radiologists on clinical imaging. RESULTS: Among 839 patients with advanced melanoma treated with ICIs, 81 had serial PET-CT scans approximately 12 months apart and long-term survival; of these 11 patients had pre-existing steatosis/steatohepatitis. Overall, ICI was not associated with significant increases in liver enzymes in all patients; modest decreases in liver enzymes were observed in patients with pre-existing steatosis/steatohepatitis. Similarly, liver attenuation did not change from baseline to post-treatment (58.44 vs 60.60 HU, + 2.17, p = 0.055). CONCLUSIONS: ICIs may not chronically affect liver enzymes or liver attenuation, a non-invasive measure of liver fat content and inflammation, in the general population or in those with pre-existing steatosis/steatohepatitis.

The ubiquitin ligase Stub1 negatively modulates regulatory T cell suppressive activity by promoting degradation of the transcription factor Foxp3.

Regulatory T (Treg) cells suppress inflammatory immune responses and autoimmunity caused by self-reactive T cells. The key Treg cell transcription factor Foxp3 is downregulated during inflammation to allow for the acquisition of effector T cell-like functions. Here, we demonstrate that stress signals elicited by proinflammatory cytokines and lipopolysaccharides lead to the degradation of Foxp3 through the action of the E3 ubiquitin ligase Stub1. Stub1 interacted with Foxp3 to promote its K48-linked polyubiquitination in an Hsp70-dependent manner. Knockdown of endogenous Stub1 or Hsp70 prevented Foxp3 degradation. Furthermore, the overexpression of Stub1 in Treg cells abrogated their ability to suppress inflammatory immune responses in vitro and in vivo and conferred a T-helper-1-cell-like phenotype. Our results demonstrate the critical role of the stress-activated Stub1-Hsp70 complex in promoting Treg cell inactivation, thus providing a potential therapeutic target for the intervention against autoimmune disease, infection, and cancer.

Building a Virtual Global Knowledge Network During the Coronavirus Disease 2019 Pandemic: The Infection Prevention and Control Global Webinar Series.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has been an unprecedented global health challenge. Traditional modes of knowledge dissemination have not been feasible. A rapid solution was needed to share guidance and implementation examples within the global infection prevention and control (IPC) community. We designed the IPC Global Webinar Series to bring together subject matter experts and IPC professionals in the fight against COVID-19. METHODS: The Extension for Community Healthcare Outcomes (ECHO) model was adapted to create an interactive global knowledge network. Speakers and panelists provided presentations and answers to questions. Webinars were simultaneously interpreted into 5 languages and recorded for later access. RESULTS: Thirteen webinar sessions were completed from 14 May through 6 August 2020. On average, 634 participants attended each session (range, 393-1181). Each session was represented by participants from, on average, more than 100 countries. CONCLUSIONS: Through the IPC Global Webinar Series, critical information was shared and peer-to-peer learning was promoted during the COVID-19 pandemic response. The webinar sessions reached a broader audience than many in-person events. The webinar series was rapidly scaled and can be rapidly reactivated as needed. Our lessons learned in designing and implementing the series can inform the design of other global health virtual knowledge networks. The continued and expanded use of adapted virtual communities of practice and other learning networks for the IPC community can serve as a valuable tool for addressing COVID-19 and other infectious disease threats.The infection prevention and control (IPC) Global Webinar Series convened subject matter experts and IPC professionals from more than 100 countries to establish a global learning community for COVID-19. We advocate for expanded use of virtual knowledge networks.

Multi-country cross-sectional study of colonization with multidrug-resistant organisms: protocol and methods for the Antibiotic Resistance in Communities and Hospitals (ARCH) studies.

BACKGROUND: Antimicrobial resistance is a global health emergency. Persons colonized with multidrug-resistant organisms (MDROs) are at risk for developing subsequent multidrug-resistant infections, as colonization represents an important precursor to invasive infection. Despite reports documenting the worldwide dissemination of MDROs, fundamental questions remain regarding the burden of resistance, metrics to measure prevalence, and determinants of spread. We describe a multi-site colonization survey protocol that aims to quantify the population-based prevalence and associated risk factors for colonization with high-threat MDROs among community dwelling participants and patients admitted to hospitals within a defined population-catchment area. METHODS: Researchers in five countries (Bangladesh, Chile, Guatemala, Kenya, and India) will conduct a cross-sectional, population-based prevalence survey consisting of a risk factor questionnaire and collection of specimens to evaluate colonization with three high-threat MDROs: extended-spectrum cephalosporin-resistant Enterobacteriaceae (ESCrE), carbapenem-resistant Enterobacteriaceae (CRE), and methicillin-resistant Staphylococcus aureus (MRSA). Healthy adults residing in a household within the sampling area will be enrolled in addition to eligible hospitalized adults. Colonizing isolates of these MDROs will be compared by multilocus sequence typing (MLST) to routinely collected invasive clinical isolates, where available, to determine potential pathogenicity. A colonizing MDRO isolate will be categorized as potentially pathogenic if the MLST pattern of the colonizing isolate matches the MLST pattern of an invasive clinical isolate. The outcomes of this study will be estimates of the population-based prevalence of colonization with ESCrE, CRE, and MRSA; determination of the proportion of colonizing ESCrE, CRE, and MRSA with pathogenic characteristics based on MLST; identification of factors independently associated with ESCrE, CRE, and MRSA colonization; and creation an archive of ESCrE, CRE, and MRSA isolates for future study. DISCUSSION: This is the first study to use a common protocol to evaluate population-based prevalence and risk factors associated with MDRO colonization among community-dwelling and hospitalized adults in multiple countries with diverse epidemiological conditions, including low- and middle-income settings. The results will be used to better describe the global epidemiology of MDROs and guide the development of mitigation strategies in both community and healthcare settings. These standardized baseline surveys can also inform future studies seeking to further characterize MDRO epidemiology globally.

Neuro-Ophthalmic Manifestations of Mollaret Meningitis.

ABSTRACT: Mollaret meningitis (MM) refers to benign recurrent aseptic meningitis usually following herpes simplex virus 2 (HSV-2) infection. Neuro-ophthalmic manifestations associated with MM are rarely reported. We present a case of recurrent HSV-2 meningitis with the neuro-ophthalmic presentation of papilledema and sixth nerve palsy. To our knowledge, this is the first such description in the English language ophthalmic literature.

Rapid Sentinel Surveillance for COVID-19 - Santa Clara County, California, March 2020.

On February 27, 2020, the Santa Clara County Public Health Department (SCCPHD) identified its first case of coronavirus disease 2019 (COVID-19) associated with probable community transmission (i.e., infection among persons without a known exposure by travel or close contact with a patient with confirmed COVID-19). At the time the investigation began, testing guidance recommended focusing on persons with clinical findings of lower respiratory illness and travel to an affected area or an epidemiologic link to a laboratory-confirmed COVID-19 case, or on persons hospitalized for severe respiratory disease and no alternative diagnosis (1). To rapidly understand the extent of COVID-19 in the community, SCCPHD, the California Department of Public Health (CDPH), and CDC began sentinel surveillance in Santa Clara County. During March 5-14, 2020, four urgent care centers in Santa Clara County participated as sentinel sites. For this investigation, county residents evaluated for respiratory symptoms (e.g., fever, cough, or shortness of breath) who had no known risk for COVID-19 were identified at participating urgent care centers. A convenience sample of specimens that tested negative for influenza virus was tested for SARS-CoV-2 RNA. Among 226 patients who met the inclusion criteria, 23% had positive test results for influenza. Among patients who had negative test results for influenza, 79 specimens were tested for SARS-CoV-2, and 11% had evidence of infection. This sentinel surveillance system helped confirm community transmission of SARS-CoV-2 in Santa Clara County. As a result of these data and an increasing number of cases with no known source of transmission, the county initiated a series of community mitigation strategies. Detection of community transmission is critical for informing response activities, including testing criteria, quarantine guidance, investigation protocols, and community mitigation measures (2). Sentinel surveillance in outpatient settings and emergency departments, implemented together with hospital-based surveillance, mortality surveillance, and serologic surveys, can provide a robust approach to monitor the epidemiology of COVID-19.

Evaluation of Infection Prevention and Control Readiness at Frontline Health Care Facilities in High-Risk Districts Bordering Ebola Virus Disease-Affected Areas in the Democratic Republic of the Congo - Uganda, 2018.

Infection prevention and control (IPC) in health care facilities is essential to protecting patients, visitors, and health care personnel from the spread of infectious diseases, including Ebola virus disease (Ebola). Patients with suspected Ebola are typically referred to specialized Ebola treatment units (ETUs), which have strict isolation and IPC protocols, for testing and treatment (1,2). However, in settings where contact tracing is inadequate, Ebola patients might first seek care at general health care facilities, which often have insufficient IPC capacity (3-6). Before 2014-2016, most Ebola outbreaks occurred in rural or nonurban communities, and the role of health care facilities as amplification points, while recognized, was limited (7,8). In contrast to these earlier outbreaks, the 2014-2016 West Africa Ebola outbreak occurred in densely populated urban areas where access to health care facilities was better, but contact tracing was generally inadequate (8). Patients with unrecognized Ebola who sought care at health care facilities with inadequate IPC initiated multiple chains of transmission, which amplified the epidemic to an extent not seen in previous Ebola outbreaks (3-5,7). Implementation of robust IPC practices in general health care facilities was critical to ending health care-associated transmission (8). In August 2018, when an Ebola outbreak was recognized in the Democratic Republic of the Congo (DRC), neighboring countries began preparing for possible introduction of Ebola, with a focus on IPC. Baseline IPC assessments conducted in frontline health care facilities in high-risk districts in Uganda found IPC gaps in screening, isolation, and notification. Based on findings, additional funds were provided for IPC, a training curriculum was developed, and other corrective actions were taken. Ebola preparedness efforts should include activities to ensure that frontline health care facilities have the IPC capacity to rapidly identify suspected Ebola cases and refer such patients for treatment to protect patients, staff members, and visitors.

Locoregional Therapy of Hepatocellular-Cholangiocarcinoma versus Hepatocellular Carcinoma: A Propensity Score-Matched Study.

PURPOSE: To compare outcomes of unresectable hepatocellular-cholangiocarcinoma (HCC-CC) with hepatocellular carcinoma (HCC) after locoregional therapy (LRT). MATERIALS AND METHODS: Consecutive patients with histologically confirmed HCC-CC or HCC treated with LRT between 2007 and 2017 were retrospectively reviewed. Ten patients (8 men; median age, 60 y) with 12 HCC-CCs (mean diameter, 4.2 cm ± 1.9; mean number, 3.7 ± 3.3) treated with chemoembolization (n = 6), yttrium-90 radioembolization (n = 2), RF ablation (n = 1), or chemoembolization/RF ablation (n = 1) were compared with 124 patients (92 men; median age, 59 y) with 134 HCCs (mean diameter, 4.8 cm ± 4.0; mean number, 2.6 ± 2.2) treated with chemoembolization (n = 51), yttrium-90 radioembolization (n = 17), RF ablation (n = 41), or chemoembolization/RF ablation (n = 15). Propensity score-matched analysis with conditional logistic regression adjusted for age, sex, LRT modality, tumor-specific features, and Child-Pugh class. Tumor-volume doubling time (TVDT) before LRT and objective response rates were compared by Kruskal-Wallis and Fisher exact test; progression-free survival (PFS) and transplant-free survival (TFS) were compared by Cox proportional hazards model. RESULTS: On univariate analysis, HCC-CC was associated with lower median TVDT (2.4 months vs 5.2 months, P = .03), objective response (30% vs 71%, P = .01), and median PFS (2.4 months vs 7.4 months, HR 4.3, 95% CI 2.2-8.4, P < .0001). Propensity score-matched analysis demonstrated greater distant progression (60% vs 30%, P = .003) and significantly shorter median PFS (2.4 months vs 6.0 months, HR 3.3, 95% CI 1.3-8.9, P = .017) for HCC-CC. No significant difference was observed in TFS (7.5 months vs 13.8 months, HR 1.5, 95% CI 0.4-6.1). CONCLUSIONS: HCC-CC was associated with reduced PFS and greater distant progression after LRT compared with HCC, indicating a need for adjunctive treatment strategies to improve outcomes.

Interlaboratory agreement of coccidioidomycosis enzyme immunoassay from two different manufacturers.

Coccidioidomycosis, a fungal infection endemic to the Southwestern United States, is challenging to diagnose. The coccidioidomycosis enzyme immunoassay (EIA) test is the least expensive and simplest to perform to detect coccidioidomycosis antibodies in the serum. Concerns regarding falsely positive immunoglobulin (Ig) M EIA test results have led to questions about the agreement of commercially available EIA test kits among laboratories. We sought to evaluate the laboratory agreement of the EIA test at three laboratories using both IMMY and Meridian EIA test kits. Sensitivity and specificity of EIA IgM and IgG were calculated as secondary outcomes. The percent agreement of the EIA IgM and IgG test results among all three laboratories was 90% and 89% for IMMY test kits, respectively, and 67% and 80.5% for Meridian test kits, respectively. Agreement between IgM and IgG combined test results was 85.5% and 70.5%, for IMMY and Meridian, respectively. Combined IgM and IgG assays demonstrated a sensitivity of 68% (62.7%-76%) and a specificity of 99.3% (98%-100%) [IMMY] and a sensitivity of 72.4% (57.3%-87.3%) and a specificity of 91.3% (74%-100%) [Meridian]. In summary, results from the IMMY EIA test kit agreed more often across laboratories than Meridian EIA results, especially for the IgM assay. Isolated positive IgM EIA results using the Meridian test kit should be interpreted with caution and consideration of clinical information and test methodology. Further study of the sensitivity and specificity of coccidioidomycosis EIA test kits is warranted.